A Rigid, Mono(Aquated) Mn(II)-Based Complex as MRI Contrast Agent for the Liver and Brain Vasculature Imaging

A new macrocyclic ligand (PCCy4A) featuring a lipophilic cyclohexylamine pendant arm and its corresponding Mn(II) complex {Na2[Mn(PCCy4A)]} have been developed. The complex exhibited high thermodynamic stability (log KMnL = 16.81 and pMn = 9.44 at [L] = [Mn] = 10-5 M, 25 °C), significant kinetic inertness [t1/2 = 63 h, at pH 6.0 (MES buffer)] when exposed to a 25-fold excess of Zn(II) ions, and excellent relaxivity (r1 = 3.14 mM-1 s-1, 1.41 T, 37 °C), which further increased 6-fold in the presence of serum albumin, demonstrating strong albumin affinity (69%; KA = 3.16 × 103 M-1). This results in a substantial boost in MRI signal intensity within the mouse brain vasculature at a dose of 0.08 mmol/kg. During T1-weighted imaging, 220% brightness enhancement was observed in the liver. Thus, Na2[Mn(PCCy4A)] was identified as a highly effective, multipurpose MRI contrast agent with the bio-friendly Mn ion.